1 The Effects of Acid Sphingomyelinase Deficiency on Male Germ Cell Development and Programmed Cell Death1

Abstract 1 2 Deficiency of acid sphingomyelinase (ASM), an enzyme responsible for producing a pro-apoptotic 3 second messenger ceramide, has previously been shown to promote the survival of fetal mouse oocytes 4 in vivo and to protect oocytes from chemotherapy-induced apoptosis in vitro. Here, we investigated the 5 effects of ASM deficiency on testicular germ cell development and on the ability of germ cells to 6 undergo apoptosis. At the age of 20 weeks ASMKO sperm concentrations were comparable to WT 7 sperm concentrations, whereas sperm motility was seriously affected. Acid sphingomyelinase knock-